Posted 08 March 2017 - 02:43 AM
I am getting tired of reading some ignorant people saying Niagen is the same as B3. Read this.
Dr. Brenner is the Roy J. Carver Chair and head of biochemistry at the University of Iowa. He's also a founding co-director of the University of Iowa Obesity Initiative. Researchers around the world have validated and added to his research providing evidence of NR's unique properties in neuroprotection, sirtuin activation, protection against weight gain on a high-fat diet, and improvement of blood glucose and insulin sensitivity. Dr. Brenner is one of five Scientific Advisors for CDXC.
The following interview explains the differences in Niacin/Nicotinic Acid/NA, Nicotinamide/NAM and Niagen/NR/Nicotinamide Riboside. I'm breaking the names out because it can get confusing given how similar they are.
Following is my interview with Dr. Charles Brenner, an expert in NAD+ and energy metabolism, a published researcher, and inventor of the NR NAD+ related patents.
Q: Thank you for taking the time to answer some questions. It is greatly appreciated, especially since I take Niagen daily along with many friends and family. Many don't understand the importance of NAD+. Would you be kind enough to take the time to explain it a bit?
Answer (Charles Brenner): NAD+ is the central mediator of metabolism. No cell can survive without it. NAD+ is required for foods to be converted to energy, for the synthesis of hormones, for DNA to be repaired, and for resistance to stresses like reactive oxygen species. NAD+ declines in aging. Our resiliency and metabolism decline in aging. Boosting NAD+ is a way to maintain youthful metabolism and youthful resiliency.
Q: Why are nicotinamide and niacin in our diet at 15 mg/day?
CB: Deficiency of vitamin B3 causes pellagra - almost no one has pellagra anymore. Low doses of nicotinamide and/or niacin prevent this deficiency.
Q: Why do some people take large doses of niacin?
CB: High doses of niacin, meaning 500 mg to 4 grams/day, improve cholesterol (HDL up, LDL down, free fatty acids down). Unfortunately, high dose niacin causes flushing, which limits its use.
High dose nicotinamide is not as commonly used. It doesn't improve cholesterol.
Q: What is the relationship between NR and NAD+?
CB: NR is one of three vitamin precursors of NAD. NAD is the master regulator of metabolism, which declines in aging. The basic thesis of NR is that NR boosts NAD+ without inhibiting sirtuins (the problem with nicotinamide), without causing flushing (the problem with niacin) and in damaged cells including nerves and muscles. Nicotinamide and niacin can't substitute for NR because they aren't used in all of the same cells and they don't produce the same results. The best example of these compounds not being equivalent is with respect to glycemic control. Nicotinamide and niacin promote insulin insensitivity (which is bad), while NR promotes insulin sensitivity (which staves off type 2 diabetes). So you should not believe anyone who says that the three compounds are equivalent.
Different cells and tissues use different pathways to make NAD. Some cells don't need a vitamin to make NAD and can make NAD by expressing eight different genes that convert the amino acid tryptophan to NAD. It turns out this is the basis for the differences between NR, niacin and nicotinamide and tryptophan. A lot of different cells need NAD. If the genes for a particular NAD precursor are not on, no amount of that precursor can help that cell make NAD.
For example, if any of the eight genes in the tryptophan pathway are not turned on in a particular type of human cell, that cell can't make NAD from any amount of tryptophan. That's part of the reason why tryptophan is such a poor NAD precursor. Tryptophan is an inefficient precursor in some cells and it's simply not an NAD precursor in other cells because the tryptophan pathway genes are off.
Niacin and nicotinamide are both very important compounds in prevention of dietary insufficiency but they cannot substitute for NR as metabolic boosters because there are different genes required to make NAD from these compounds.
Q: The article I asked you to read stated that "All three produce NAD+ in the human body." Please elaborate on this.
CB: There are trillions of cells in the human body of many hundreds of cell types. For example, there are nerve cells, skeletal muscle cells, cardiac cells, several types of pancreatic cells, several types of blood cells, liver cells, etc. What makes a neuron a neuron and not a hepatocyte is the expression of neuronal genes. When we discovered NR as a vitamin, we discovered the NR pathway to NAD. The value proposition of NR depends on the unique ability of NR to maintain and boost NAD in every cell and tissue and, in particular, in tissues undergoing damage and stress.
There are only two steps in the NR pathway to NAD but there are two genes that can do the first step and three genes that can do the second step. The NR pathway never gets turned off. NRK1 is expressed in every cell and tissue, while NRK2 is turned on by cellular damage, particularly in skeletal and cardiac muscle. This means that people supplementing with NR are able to keep NAD levels high in stressed cells that specifically have the NR pathway turned on to deal with cellular stress. Supplementing with niacin and nicotinamide doesn't help because they don't feed into the NR pathway, which is turned on by stresses.
Q: What's the problem with niacin or nicotinamide as a NAD+ precursor?
CB: There are three problems with niacin and two problems with nicotinamide, particularly at high doses.
First, niacin can't be used in lots of tissues because the niacin pathway is not on. The brain and skeletal muscle can't use niacin to boost NAD and these are two of the most important tissues that suffer the ravages of aging. Niacin also causes flushing at high doses and does not efficiently elevate mitochondrial NAD.
The nicotinamide pathway declines in aging, which means you would need ever higher doses to try to maintain your NAD. Second, at high doses, nicotinamide inhibits sirtuins, which is the opposite of NR. NR is a STAC that extends lifespan in model systems.
Q: Can you give me some clarification on model systems?
CB: Basically, we are talking about yeast, flies, worms and rodents - systems in which scientists have total control over the genetics, environment and diet and can carefully look at results. In yeast, nicotinamide shortens lifespan. NR extends yeast lifespan even when they are on a high sugar diet.
In mice and people, both nicotinamide and niacin can induce insulin resistance, which is a precursor to diabetes. NR promotes insulin sensitivity and resistance to diabetic neuropathy. The previous blog on Seeking Alpha suggested that people could take either nicotinamide or niacin to get the same benefits of NR. That's just utterly inconsistent with facts. NR is a STAC - to my knowledge the only bona fide one in the marketplace - I don't count resveratrol because that has been pretty much debunked. Nicotinamide is a sirtuin inhibitor and niacin can't contribute to brain or muscle NAD.
Q: The previous article did some calculations about the efficiency of NR versus nicotinamide and niacin, justifying why the individual wanted to take particular amounts of low cost vitamins in place of NR. You were the senior author of the clinical study. Were those calculations correct?
CB: No. The Seeking Alpha blogger did a calculation of how much more nicotinamide or niacin in order to have the activity of NR in a mouse's liver. The paper is here.
It's well known that niacin and nicotinamide work in liver. The problem again is niacin can't be used by muscle or brain and that damaged tissues induce the NR pathway in order to maintain function. Niacin isn't used by all tissues and high dose nicotinamide inhibits sirtuins. His premise was false because it was based on liver data. He's not going to get any benefit to damaged nerves or muscle so his idea is simply invalid.
NR is the only NAD-boosting compound that elevates metabolism, protects damaged nerves, extends lifespan in mice and other model systems, and increases insulin sensitivity. Inexpensive NAD precursors are not STACs and cannot substitute for NR. We are dealing with an aging population with a high incidence of chronic diseases that involve inflammation, insulin insensitivity, neuropathy and heart diseases, all of which can potentially be addressed uniquely by NR. You can be assured that there is no other NAD precursor that can do what NR does.
Having Dr. Brenner take the time to explain a bit more about Niagen was very helpful. It's clear that its benefits can't be duplicated by the other B vitamins.
Published research is demonstrating NR is an effective NAD+ precursor in slowing or stopping neuronal cell death associated with NAD+ depletion. Not only does Niagen appear to be an anti-aging ingredient, there is research being published showing neuroprotection. Following are some highlights.
Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection:
Additional studies with nicotinamide riboside in models of Alzheimer's disease indicate bioavailability to brain and protective effects, likely by stimulation of brain NAD synthesis.
Dr. Jeffrey Milbrandt published a study titled SARM1 activation triggers axon degeneration locally via NAD+ destruction. This study clearly shows the harm when NAD+ is low.
Along the same lines as the study Dr. Milbrandt published is one titled "Neuronal death induced by misfolded prion protein is due to NAD+ depletion and can be relieved in-vitro and in-vivo by NAD+ replenishment":
We propose the development of NAD(+) replenishment strategies for neuroprotection in prion diseases and possibly other protein misfolding neurodegenerative diseases.
Of the ongoing and upcoming human clinical trials of NR, several of them deal with neuroprotection. Thorne Research and the Mayo Clinic are running a trial dealing with concussion. Kansas University will be running an Alzheimer's Disease trial. UT Health Science Center in Texas will run one dealing with Mild Cognitive Impairment. These will be interesting trials to watch.
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